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Article: Mutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes
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TitleMutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes
 
AuthorsYu, G3 2
Chen, F3 2
Nishimura, M3 2
Steiner, H1
Tandon, A3 2
Kawarai, T3 2
Arawaka, S3 2
Supala, A3 2
Song, YQ3 2
Rogaeva, E3 2
Holmes, E3 2
Zhang, DM3 2
Milman, P3 2
Fraser, P3 2
Haass, C1
St GeorgeHyslop, P3 2
 
Keywordsγ-secretase
Alzheimer disease
Amyloid β-peptide
Presenilin complexes
 
Issue Date2000
 
PublisherBlackwell Munksgaard
 
CitationActa Neurologica Scandinavica, Supplement, 2000, v. 102 n. 176, p. 6-11 [How to Cite?]
DOI: http://dx.doi.org/10.1034/j.1600-0404.2000.00301.x
 
AbstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments (NTF/CTF). Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of APP and Notch. We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes. Aspartate-mutant presenilin holo-proteins also preclude entry of endogenous wild-type PS1/PS2 into the high molecular weight complexes, but do not affect the incorporation of wild-type holoproteins into lower molecular weight holoprotein complexes. These data suggest that the loss-of-function aspartate-mutants cause altered PS complex maturation, and argue that the functional presenilin moieties are contained in the high molecular weight presenilin NTF/CTF-containing complexes.
 
ISSN0065-1427
2012 SCImago Journal Rankings: 0.335
 
DOIhttp://dx.doi.org/10.1034/j.1600-0404.2000.00301.x
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYu, G
 
dc.contributor.authorChen, F
 
dc.contributor.authorNishimura, M
 
dc.contributor.authorSteiner, H
 
dc.contributor.authorTandon, A
 
dc.contributor.authorKawarai, T
 
dc.contributor.authorArawaka, S
 
dc.contributor.authorSupala, A
 
dc.contributor.authorSong, YQ
 
dc.contributor.authorRogaeva, E
 
dc.contributor.authorHolmes, E
 
dc.contributor.authorZhang, DM
 
dc.contributor.authorMilman, P
 
dc.contributor.authorFraser, P
 
dc.contributor.authorHaass, C
 
dc.contributor.authorSt GeorgeHyslop, P
 
dc.date.accessioned2011-07-14T07:02:50Z
 
dc.date.available2011-07-14T07:02:50Z
 
dc.date.issued2000
 
dc.description.abstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments (NTF/CTF). Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of APP and Notch. We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes. Aspartate-mutant presenilin holo-proteins also preclude entry of endogenous wild-type PS1/PS2 into the high molecular weight complexes, but do not affect the incorporation of wild-type holoproteins into lower molecular weight holoprotein complexes. These data suggest that the loss-of-function aspartate-mutants cause altered PS complex maturation, and argue that the functional presenilin moieties are contained in the high molecular weight presenilin NTF/CTF-containing complexes.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationActa Neurologica Scandinavica, Supplement, 2000, v. 102 n. 176, p. 6-11 [How to Cite?]
DOI: http://dx.doi.org/10.1034/j.1600-0404.2000.00301.x
 
dc.identifier.doihttp://dx.doi.org/10.1034/j.1600-0404.2000.00301.x
 
dc.identifier.epage11
 
dc.identifier.issn0065-1427
2012 SCImago Journal Rankings: 0.335
 
dc.identifier.issue176
 
dc.identifier.pmid11261807
 
dc.identifier.scopuseid_2-s2.0-0034571441
 
dc.identifier.spage6
 
dc.identifier.urihttp://hdl.handle.net/10722/134757
 
dc.identifier.volume102
 
dc.publisherBlackwell Munksgaard
 
dc.publisher.placeDenmark
 
dc.relation.ispartofActa Neurologica Scandinavica, Supplement
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAlzheimer Disease/*physiopathology
 
dc.subject.meshAmyloid Precursor Protein Secretases
 
dc.subject.meshAmyloid beta-Peptides/metabolism
 
dc.subject.meshAnimals
 
dc.subject.meshAspartic Acid/analogs & derivatives/genetics/*metabolism
 
dc.subject.meshAspartic Acid Endopeptidases
 
dc.subject.meshCell Culture Techniques
 
dc.subject.meshCell Membrane
 
dc.subject.meshDNA, Complementary/genetics
 
dc.subject.meshEndopeptidases/metabolism
 
dc.subject.meshGene Expression Regulation
 
dc.subject.meshHumans
 
dc.subject.meshMembrane Proteins/*genetics/metabolism
 
dc.subject.meshMice
 
dc.subject.mesh*Point Mutation
 
dc.subject.meshPresenilin-1
 
dc.subject.meshPresenilin-2
 
dc.subject.meshProtein Conformation
 
dc.subjectγ-secretase
 
dc.subjectAlzheimer disease
 
dc.subjectAmyloid β-peptide
 
dc.subjectPresenilin complexes
 
dc.titleMutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes
 
dc.typeArticle
 
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<contributor.author>Kawarai, T</contributor.author>
<contributor.author>Arawaka, S</contributor.author>
<contributor.author>Supala, A</contributor.author>
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Author Affiliations
  1. Adolf-Butenandt-Institut
  2. Toronto Western Hospital University of Toronto
  3. University of Toronto